Deficiencies of MutL DNA mismatch repair-complex proteins (hMLH1, hPMS2, and hPMS1) typically result in microsatellite instability in human cancers. We examined the association patterns of MutL proteins in human epithelial cancer cell lines with (HCT-116, N87, SNU-1, and SNU-638) and without microsatellite instability (HeLa, AGS, KATO-III, and SNU-16). The analysis of hMLH1, hPMS2, and hPMS1 was performed using Northern blot, Western blot, and co-immunoprecipitation studies. Our data provide evidence that MutL proteins form two different complexes, MutL-α (hPMS2 and hMLH1) and MutL-β (hPMS1 and hMLH1). Gastric and colorectal cancer cells lines with microsatellite instability lacked detectable hMLH1. Decreased levels of hMLH1 protein were associated with markedly reduced levels of hPMS2 and hPMS1 proteins, but the RNA levels of hPMS1 and hPMS2 were normal. In this study, we describe the association of hPMS1 with hMLH1 as a heterodimer, in human cells. Furthermore, normal levels of hMLH1 protein appear to be important in maintaining normal levels of hPMS1 and hPMS2 proteins.

Deficiencies of MutL DNA mismatch repair-complex proteins (hMLH1, hPMS2, and hPMS1) typically result in microsatellite instability in human cancers. We examined the association patterns of MutL proteins in human epithelial cancer cell lines with (HCT-116, N87, SNU-1, and SNU-638) and without microsatellite instability (HeLa, AGS, KATO-III, and SNU-16). The analysis of hMLH1, hPMS2, and hPMS1 was performed using Northern blot, Western blot, and co-immunoprecipitation studies. Our data provide evidence that MutL proteins form two different complexes, MutL-α (hPMS2 and hMLH1) and MutL-β (hPMS1 and hMLH1). Gastric and colorectal cancer cells lines with microsatellite instability lacked detectable hMLH1. Decreased levels of hMLH1 protein were associated with markedly reduced levels of hPMS2 and hPMS1 proteins, but the RNA levels of hPMS1 and hPMS2 were normal. In this study, we describe the association of hPMS1 with hMLH1 as a heterodimer, in human cells. Furthermore, normal levels of hMLH1 protein appear to be important in maintaining normal levels of hPMS1 and hPMS2 proteins.

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eng

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American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/

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Journal of Biological Chemistry

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Adaptor Proteins, Signal Transducing

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Adenosine Triphosphatases

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Base Pair Mismatch - Genetics

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Carrier Proteins - Genetics - Metabolism

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Dna Repair - Genetics

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Dna Repair Enzymes

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Dna-Binding Proteins

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Dimerization

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Gene Expression Regulation, Neoplastic

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Humans

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Microsatellite Repeats - Genetics

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Neoplasm Proteins - Genetics - Metabolism

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Nuclear Proteins

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Precipitin Tests

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Proteins - Genetics - Metabolism

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Rna, Messenger - Metabolism

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Tumor Cells, Cultured

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dc.title

Identification of a second MutL DNA mismatch repair complex (hPMS1 and hMLH1) in human epithelial cells